We aimed to evaluate whether proteinuria and estimated glomerular filtration rate (eGFR) levels can modify the efficacy of folic acid therapy on the risk of all-cause mortality among hypertensive patients in the China Stroke Primary Prevention Trial, a randomized, double-blind, and controlled trial.Methods:
A total of 20 702 hypertensive patients without a history of major cardiovascular diseases were randomly assigned to a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n = 10 348), or 10-mg enalapril alone (n = 10 354). All-cause mortality, a prespecified endpoint of the China Stroke Primary Prevention Trial, was the main outcome in this analysis.Results:
Over a median treatment duration of 4.5 years, in the enalapril alone group, both heavy proteinuria [vs. absent, 10.8 vs. 2.7%; hazard ratio = 3.30; 95% confidence interval (CI): 2.10–5.18] and lower eGFR levels (<60 vs. ≥90 ml/min per 1.73 m2, 13.0 vs. 2.2%; hazard ratio = 1.93; 95% CI: 1.19–3.12) were significantly associated with increased risk of all-cause mortality. Folic acid supplementation significantly reduced the risk of all-cause mortality in patients with heavy proteinuria (6.4% in the enalapril-folic acid vs. 10.8% in the enalapril alone group, hazard ratio = 0.49; 95% CI: 0.26–0.94), but not in those with absent or mild proteinuria (2.8 vs. 2.9%, hazard ratio = 0.99; 95% CI: 0.84–1.17; P for interaction = 0.040). However, eGFR levels did not significantly modify the effect of folic acid supplementation in reducing the risk of all-cause mortality (P for interaction = 0.228).Conclusion:
Among hypertensive patients without a history of major cardiovascular diseases, folic acid therapy could reduce the mortality risk associated with heavy proteinuria.